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KMID : 0855520070200030225
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Korean Journal of Physical Anthropology
2007 Volume.20 No. 3 p.225 ~ p.233
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CD98 Activation Increases the Invasion of Human Breast Carcinoma MCF-7 Cells
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Kim Sun-Mi
Jeon Joon-Seong
Hahn Jang-Hee
Park Jeong-Hyun
Park Kyoung-Han
Kim Dae-Joong
Kim Jae-Myoung
Ahn Zoon-Seog
Kim Dae-Young
Suh Jae-Sung
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Abstract
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CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates the func-tions of β₁ integrin, suggesting that it may play a role in tumor cell invasion. In this study, the effects of CD98 signaling on the adhesion and invasion of tumor cells were investigated.
The expression of CD98 on MCF-7 human breast carcinoma cells was confirmed by immunohistochemistry. The effects of CD98 activation on the adhesion to extracellular matrix (ECM) and invasion of MCF-7 cells were determined by adhesion assay and cell invasion assay. Dominant negative forms of focal adhesion kinase (FAK) were transiently transfected into MCF-7 cells using liposome reagents.
CD98 stimulation increased the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV. Activation of CD98 augmented the invasion rate of MCF-7 cells through ECM. EDTA or a function-blocking anti-β₁ integrin mAb suppressed the effect of CD98 on invasiveness. Inhibition of phosphorylation of FAK by PP2, an inhibitor of Src family kinase, reduced CD98-induced invasion of MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, cytochalasin D or phalloidin inhibited CD98-mediated induction of tumor cell invasion. Inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated invasion of MCF-7 cells were diminished by pretreatment of cells with Mn??, which is shown to induce conformational change of β₁ intgerin.
These results provide the first evidence that CD98 activation increases tumor cell invasion by activating β₁ integrin affinity, and that FAK phosphorylation and subsequent cytoskeletal reorganization may be essential for CD98-mediated regulation of cell motility.
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KEYWORD
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CD98, β₁ integrin, Tumor cell invasion, Cell-ECM adhesion, FAK, Actin, Cytoskeleton
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